The objectives of this research involve the characterization and application of heme proteins, heme protein microspheres, and synthetic analogs of heme proteins. The focus is on inter-molecular interactions in three areas: (1) molecular recognition in ligation, sensing and catalysis; (2) porphyrin assemblies, both as covalently linked and as molecular engineered solids, and (3) heme protein assemblies, specifically protein microspheres prepared sonochemically. The chemical reactivities of interest include ligand and peptide binding to heme proteins and metalloporphyrins, oxygen activation and hydrocarbon oxidation by metalloporphyrins, and the interactions between porphyrins as redox partners in organized media. The heme proteins are relevant to cardiovascular functioning; to drug, hormone, and exobiotic metabolism; to oxidant detoxification and substrate oxidation; and to biological electron transfer and photosynthesis. Some of this research provides a fundamental understanding of the molecular mechanisms of heme protein reactivity, using closely related model metalloporphyrins and peptide-heme complexes acting as synthetic heme proteins. The group is exploring molecular recognition and substrate specificity, the nature of heme-peptide and heme-heme interactions, and the chemical and photochemical generation of highly oxidized iron porphyrin complexes. In related work, it has been discovered that ultrasonic irradiation of various proteins (e.g., hemoglobin and serum albumin) creates micron-sized spheres. These microspheres have a very thin shell of crosslinked protein with either a gas- or liquid-filled core. These have been used with substantial success as biocompatible medical diagnostic imaging agents, e.g., as functional magnetic resonance imaging spin-label probes for in vivo O2 and temperature profiling. Microspheres made of Hb and of other proteins are currently under development and animal testing as O2 carrying pharmaceuticals. Continuation of efforts in these areas should lead to (1) the development of a new class of biocompatible microencapsulation for drug and O2 delivery and diagnostic imaging, (2) a quantitative understanding of the influences which modulate ligand binding in protein environments, (3) further characterization of the reactivity of high-oxidation state heme protein intermediates (4) a closer understanding of substrate selectivity and regiospecificity by monooxygenases, and (5) basic knowledge about porphyrin-porphyrin interactions in pi-overlapping systems such as the photosynthetic reaction center.